FDA wants more respect and less second-guessing of its regulatory actions. The strategy is to build in-house scientific expertise
and improve evaluation methods so that a decision to approve a drug for market—or to require postmarketing studies—doesn't
draw criticism on the political front or challenges from experts with differing opinions.
Strengthening FDA's science base has been a leading theme for Commissioner Margaret Hamburg since she took the helm at the
agency a year ago. Hamburg has gained modest recognition for this effort from the Obama administration, which earmarked money
for a small science program in the 2011 budget plan, and from the National Institutes of Health (NIH), which is funding research
on ways to improve the science of evaluating new drug safety and efficacy.
Up until now, the field of regulatory science has not received the resources, or the intellectual energy, that it deserves,
Hamburg stated in announcing the FDA-NIH collaboration in February. "We have allowed the arm of regulatory science to become
weak and under-developed," she said, adding that if this situation is not fixed "we will row in circles."
Discoveries and Investment
Hamburg and others are dismayed that the nation's huge investment in biomedical research, epitomized by decoding the human
genome, has not translated into important new treatments. For that to happen, Hamburg stated at a February meeting of the
Personalized Medicine Coalition (PMC), biomedical discoveries "must be married to a robust investment in regulatory science."
This includes developing new tools and standards to assess medical product safety, effectiveness, potency, quality, and performance.
Hamburg is looking for standards for novel cell-based therapies, reagents to test flu vaccine potency, and strategies for
screening compounds for serious adverse events, among other advances.
Regulatory science is key to advancing personalized medicine by providing the research community with a better understanding
of the genetics of drug metabolism and an idea of which patients may be at risk for adverse effects from a particular drug,
Hamburg explained. The discovery of genetic markers, for example, has led to labeling to prevent use of certain colon cancer
drugs by patients with the K-RAS mutation, who are unlikely to benefit. And biomarker validation projects have produced new
rodent assays that can pick up early signs of kidney toxicity.
Hamburg promises to issue long-awaited draft guidance this year on biomarker qualification and the co-development of drugs
and diagnostics. At the same time, the commissioner is seeking agreement across FDA centers about the kind of evidence needed
to rely on a test result to shape a drug trial, or product approval and relabeling. Hamburg also plans more guidance on clinical
trial design—particularly for smaller trials—and more flexible endpoints for rare disease treatments.
Leverage and Collaboration
Because FDA has very limited resources to expand its scientific capabilities, Hamburg is looking for assistance from other
government agencies and from industry. In February, Health and Human Services (HHS) secretary Kathleen Sebelius joined Hamburg
and NIH director Francis Collins in announcing a collaborative effort to promote regulatory science and ensure speedier patient
access to therapies. The three-year, $6.75 million program is tiny by NIH standards, but won praise as an important first
step towards developing new approaches to biomedical product development. NIH and FDA are providing $2 million and $250,000
each year, respectively, which will support two or three annual grants to academic researchers.
Collins and Hamburg will co-chair a Joint Leadership Council composed of leading scientists from both agencies. The council
will define the research agenda with help from the broader research community at a public meeting this spring. The panel also
will encourage NIH officials to consider regulatory issues in building the institute's research programs, and seek to integrate
the latest science into FDA's review process.
Many of these issues were examined at a workshop sponsored by the Institute of Medicine (IOM) Drug Forum in late February.
That group has been discussing the need to improve FDA's science base since it issued a 2007 report on drug safety, which
highlighted this gap in agency expertise. Hamburg noted that FDA's partnership with NIH might provide a model for similar
relationships with other government agencies, such as the National Institute of Science & Technology (NIST) and HHS' Biomedical
Advanced Research & Development Authority (BARDA).